Bone Abstracts

Objectives: Glucagon-like peptide 1 is secreted by intestinal L-cells into the blood supply in response to nutrients in the intestine. Although osteoblasts express the GLP-1 receptor (GLP-1R), the main action of the GLP-1/GLP-1R pathway in bone physiology and bone quality is unknown. The aim of the present study was to investigate bone strength and quality in a mouse model of GLP-1R deficiency.

Materials/methods: Eight 16 weeks-old GLP-1R knock-out male mice, with a deletion of two exons of the glp1r gene, were age- and sex-matched with 12 wild-type (WT) mice. Resistance to fracture was studied by three-point bending in femur, whilst cortical microarchitecture was determined by high resolution microCT and quantitative X-ray imaging. Intrinsic material properties were investigated by nanoindentation. Bone mineral and collagen properties were assessed by quantitative backscattered electron imaging (qBEI) and Fourier-transformed infrared microscopy (FTIRM). Non-parametric Mann–Whitney U test was used to compare differences between groups.

Results: As compared with control mice, GLP-1R KO animals exhibited reduced bone strength as evidenced by significant decreases in ultimate load (−17%) and absorbed energy (−34%). Cortical microarchitecture was also affected in GLP-1R-deficient mice as demonstrated by significant reductions in cortical thickness (−13%) and cross-sectional moment of inertia (−25%). These microarchitectural modifications were accompanied by alterations of intrinsic material properties. Maximal load and hardness as assessed by nanoindentation on hydrated bone were both significantly reduced by 19%. Interestingly, bone mineral density distribution was not affected by GLP-1R deletion, but the ratio of mature/immature collagen cross-links was significantly reduced by 15%.

Conclusion: The inactivation of the GLP-1/GLP-1R pathway resulted in marked alterations of cortical microarchitecture, bone matrix properties and bone strength. Overall these data support an important role for the GLP-1/GLP-1R signalling pathway in bone quality. This is important given the recent introduction of GLP-1 mimetics for the treatment of type 2 diabetes mellitus.